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Review
. 2024 Feb 10;24(1):104.
doi: 10.1186/s12887-023-04442-y.

A novel variant of DNM1L expanding the clinical phenotypic spectrum: a case report and literature review

Zhenkun Zhang #  1 , Xiaofan Bie #  1 , Zhehui Chen  2 , Jing Liu  1 , Zhenhua Xie  1 , Xian Li  1 , Mengjun Xiao  1 , Qiang Zhang  1 , Yaodong Zhang  1 , Yanling Yang  3 , Dongxiao Li  4
Affiliations
Review

A novel variant of DNM1L expanding the clinical phenotypic spectrum: a case report and literature review

Zhenkun Zhang et al. BMC Pediatr. .

Abstract

Background: Mitochondrial diseases are heterogeneous in terms of clinical manifestations and genetic characteristics. The dynamin 1-like gene (DNM1L) encodes dynamin-related protein 1 (DRP1), a member of the GTPases dynamin superfamily responsible for mitochondrial and peroxisomal fission. DNM1L variants can lead to mitochondrial fission dysfunction.

Case presentation: Herein, we report a distinctive clinical phenotype associated with a novel variant of DNM1L and review the relevant literature. A 5-year-old girl presented with paroxysmal hemiplegia, astigmatism, and strabismus. Levocarnitine and coenzyme Q10 supplement showed good efficacy. Based on the patient's clinical data, trio whole-exome sequencing (trio-WES) and mtDNA sequencing were performed to identify the potential causative genes, and Sanger sequencing was used to validate the specific variation in the proband and her family members. The results showed a novel de novo heterozygous nonsense variant in exon 20 of the DNM1L gene, c.2161C>T, p.Gln721Ter, which is predicted to be a pathogenic variant according to the ACMG guidelines. The proband has a previously undescribed clinical manifestation, namely hemiparesis, which may be an additional feature of the growing phenotypic spectrum of DNM1L-related diseases.

Conclusion: Our findings elucidate a novel variant in DNM1L-related disease and reveal an expanding phenotypic spectrum associated with DNM1L variants. This report highlights the necessity of next generation sequencing for early diagnosis of patients, and that further clinical phenotypic and genotypic analysis may help to improve the understanding of DNM1L-related diseases.

Keywords: DNM1L gene; Mitochondrial diseases; Nonsense variant; Phenotypic spectrum.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Family pedigree and results of the variant in the DNM1L gene of the proband (II-2). Sanger sequencing confirmed the presence of the heterozygous variant c.2161C>T, p.Gln721Ter in the proband compared to the wild type sequence in the parents
Fig. 2
Fig. 2
Genetic location of DNM1L gene variants associated with mitochondrial diseases identified to date. A Schematic representation of the location of identified variants in each domain of the DRP1 protein. Changes in amino acid distribution associated with protein domains. Variants reported in this study are shown in red, and “x” indicates the number of cases. B The number of previously reported variants in each domain. C Comparison of the amino acid sequences of the DRP1 protein in different species. The amino acid sequence of the variant site is highly conserved (red font)
See this image and copyright information in PMC

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